Viral and fungal infections and some cancers may be described as disea
ses that are characterized by the expression of certain unwanted prote
ins. They could be termed induced genetic disorders, with induction pr
ovided by mutation or infection. A comprehensive method to inactivate
injurious genes based on their nucleic acid sequences has the potentia
l to provide effective antiviral and anticancer agents with greatly re
duced side effects. We describe a chemical approach to such gene-speci
fic pharmaceutical agents. Our initial efforts have been to develop ne
w chemical reagents that can carry out catalytic destruction of specif
ic mRNA sequences. We chose hydrolysis as a chemical means of destruct
ion, because hydrolysis is compatible with living cells. Our sequence-
specific catalytic RNA hydrolysis reagents may be described as functio
nal ribozyme mimics. Reactivity is provided by small-molecule catalyst
s, such as metal complexes. Specificity is provided by oligonucleotide
probes. Here we report initial results on the sequence-specific, hydr
olytic cleavage of mRNA from the HIV gag gene, using a ribozyme mimic.
The reagent is composed of a terpyridylCu(II) complex for cleavage ac
tivity and an oligonucleotide for sequence specificity.